The Missouri Alcoholism Research Center (MARC) has grown out of inter- linked research collaborations between alcoholism researchers at Washington University School of Medicine (the lead institution), St. Louis University, the University of Missouri, Columbia, the Palo Alto Veterans Administration Medical Center, and Queensland Institute of Medical Research, Australia. The broad focus of the research program of the MARC concerns the etiology and course of alcohol problems and associated co-morbidity in community samples of adolescents and youth. Center-wide research involves testing three classes of mediational models for alcoholism risk-pharmacological vulnerability; negative affect-regulation; deviance proneness-in a series of prospective behavioral genetic and family studies, as well as laboratory-based studies, the represent a unique combination of psychosocial, behavioral genetic, epidemiologic and experimental approaches. The Center is organized as (i) an administrative core, (ii) aa modest pilot project core, (iii) three scientific cores-the assessment (AC) core, ascertainment, tracing and tracking (ATT) core, the and the data- management and methodology and methodology (DMM) core-which provide critical support for the Center research projects; and (iv) four research projects: a) a prospective high-risk study of Missouri-born adolescent and young adult twin pairs aimed at identifying mediators or modifiers of genetic or environmental influences on alcoholism risk, including gender differences in mediators and risk-modifiers of genetic or environmental influences on alcoholism risk, including gender differences in mediators and risk-modifiers; b) a prospective family study of Missouri adolescents and youth and their siblings, including African-American families, which is designed to establish a paradigm for epidemiologic family studies and will provide important information about sibling and peer influences; c) a laboratory study of the postural effects of alcohol and nicotine administered separately and jointly; and d) a pseudo-adoption study, involving the prospective assessment of the adolescent offspring of alcoholic and control mothers from Australian twin panel, and their MZ or DZ twin sisters, which will permit tests of key environmental mediation hypothesis while avoiding the under- representation of high-risk environments associated with the traditional adoption paradigm. Despite the high economic and personal costs of alcohol misuse and associated co-morbidity in adolescents and youth, the underlying etiologic mechanisms have been little investigated undertaking such an investigation is a goal that is the unifying theme of the MARC.